We conducted a cross-sectional analysis to evaluate the relationship between serum antibody titers against 19 selected oral microorganisms and measures of hyperglycemia in a large, nationally representative data set. The study population consisted of 7,848 participants from the National Health and Nutrition Examination Survey III (1988-1994) who were at least 40 yrs old, with complete serum IgG antibody data against 19 oral microorganisms. The 19 antibody titers were grouped into 4 categories via cluster analysis--orange-red, yellow-orange, orange-blue, and red-green--named to reflect predominant antibody titers against microorganisms in Socransky's classification scheme for oral microbes. Linear regression models weighted for complex survey design were used in which fasting blood glucose, fasting insulin, and HbA1c were outcomes and antibody cluster scores were exposures, adjusting for potential confounders. Higher orange-red cluster scores were associated with increased hyperglycemia, while higher orange-blue cluster scores were related with decreased hyperglycemia. A 1-unit-higher orange-red cluster score was associated with 0.46 mg/dL higher fasting blood glucose (p = .0038), and a 1-unit-higher orange-blue cluster score was associated with 0.34% lower HbA1c (p = .0257). Groups of antibody titers against periodontal microorganisms were associated with hyperglycemia independent of known risk factors.

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Identifying factors that influence fetal growth in a sex-specific manner can help unravel mechanisms that explain sex differences in adverse neonatal outcomes and in-utero origins of cardiovascular disease disparities. Premature aging of the placenta, a tissue that supports fetal growth and exhibits sex-specific epigenetic changes, is associated with pregnancy complications. Using DNA methylation-based age estimator, we investigated the sex-specific relationship of placental epigenetic aging with fetal growth across 13-40 weeks gestation, neonatal size, and risk of low birth weight. Placental epigenetic age acceleration (PAA), the difference between DNA methylation age and gestational age, was associated with reduced fetal weight among males but with increased fetal weight among females. PAA was inversely associated with fetal weight, abdominal circumference, and biparietal diameter at 32-40 weeks among males but was positively associated with all growth measures among females across 13-40 weeks. A 1-week increase in PAA was associated with 2-fold (95% CI 1.2, 3.2) increased odds for low birth weight and 1.5-fold (95% CI 1.1, 2.0) increased odds for small-for-gestational age among males. In all, fetal growth was significantly reduced in males but not females exposed to a rapidly aging placenta. Epigenetic aging of the placenta may underlie sex differences in neonatal outcomes.